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  • 1.  Placebo Question

    This message was posted by a user wishing to remain anonymous
    Posted 28-Apr-2021 12:52
    This message was posted by a user wishing to remain anonymous

    If placebo is being used for a proof of concept phase 2a study for safety and early indications of efficacy signals, does CMC need to have  and "analytical placebo" which has the same formulation as the DP (without API) or can they do something more generic that has the exact same look and weight as the DP (not the exact same composition otherwise)?  Knowing that information on the placebo will be submitted and the ID of the placebo shall be distinguished from actual drug oral formulation, etc, I assume this is acceptable?



  • 2.  RE: Placebo Question

    Posted 29-Apr-2021 07:28
    I guess the question is: why create a non-standard "placebo"? This new "placebo" chemistry may create issues unrelated to your drug. If possible, I would recommend sticking to using the placebo intended - exact same chemistry as drug without the API. The reason we do this is to rule out effects of the drug chemistry used with the API in our human trial data. This is also why we need to send specific drug and placebo CMC data in with each application: to specifically document the two chemistries. Using a non-standard "placebo" may interfere with your ability to interpret your data. Best to have a really strong rationale if you choose to use a non-standard "placebo" for your trial and carefully describe the limits imposed on your data interpretations due to this choice of non-standard "placebo"...  for example, how will your stats work if you do not have an appropriate placebo for the control part of your trial?  What are you controlling exactly if not the chemistry of your drug? ETC, etc.

    ------------------------------
    Joy Frestedt PHD, CPI, RAC, FRAPS, FACRP
    President and CEO
    Frestedt Incorporated (www.frestedt.com)
    Saint Louis Park MN
    United States
    612-219-9982
    jf@frestedt.com
    ------------------------------

    Original Message


  • 3.  RE: Placebo Question

    Posted 29-Apr-2021 08:21
    While ideal, it is not a regulatory requirement that the placebo have the same formulation as the active product. There are many factors to consider in choosing the placebo formulation and is influenced by whether it is an oral or parenteral product, and could go beyond the standard look, taste and feel of the product. In her note, Joy summarized it well, and I would just add that there needs to be a careful analysis of how the placebo choice will influence blinding of the study and potential affects on interpretation of both safety and efficacy results.

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    Glen Park PharmD
    Vice President, Regulatory Affairs and Quality Assurance
    Scynexis, Inc.
    New York NY
    United States
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    Original Message


  • 4.  RE: Placebo Question

    This message was posted by a user wishing to remain anonymous
    Posted 29-Apr-2021 08:34
    This message was posted by a user wishing to remain anonymous

    Has to be same as the test drug without the API
    Original Message


  • 5.  RE: Placebo Question

    Posted 29-Apr-2021 09:48
    Although i think it is typical that firms use the same formulation without APi, I think you are fine with a generic placebo provided same appearance and weight as the DP .. Of course, you need to be aware of any potential effects of the excipients, e.g. would not want to include lactose (as lactose intolerant patients). I know of one large pharmaceutical company that uses the same IR tablet placebo formulation  for all their clinical trials (involving IR tablets) regardless of the formulation of the clinical formulation.

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    Robert Blanks RAC
    VP, Regulatory Affairs and Quality Assurance
    [Ardelyx]
    Auburndale MA
    United States
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    Original Message


  • 6.  RE: Placebo Question

    This message was posted by a user wishing to remain anonymous
    Posted 29-Apr-2021 18:03
    This message was posted by a user wishing to remain anonymous

    "To achieve the purpose of blinding, the characteristics of the real drug and placebo should be identical in color, appearance, smell and taste. The quality placebo should be identical to the real drug in physical form, sensory perception, packaging, and labeling, and it should have no pharmaceutical activity."

    How can someone easily achieve the above goal is to prepare a placebo with identical formulation as the active test drug minus the drug substance! Else the smell or taste may differ! 
    Original Message


  • 7.  RE: Placebo Question

    This message was posted by a user wishing to remain anonymous
    Posted 29-Apr-2021 18:03
    This message was posted by a user wishing to remain anonymous

    So, What I am hearing from the responses is that there is not a requirement to do so, but the rationale would have to be submitted along with the submission; there is added risk with potential to introduce anticipated issues with a placebo that is not identical (minus API) both in effects and in blinding -and why introduce that risk. Thank you for your feedback.
    Original Message


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